Impact of Time-of-Flight and Point-Spread-Function for Respiratory Artifact Reduction in PET/CT Imaging: Focus on Standardized Uptake Value

Background: The most important advantage of positron emission tomography/computed tomography (PET/CT) imaging is its capability of quantitative analysis. The aim of the current study was to choose the proper standardized uptake value (SUV) threshold, when the time-of-flight (TOF) and point spread function (PSF) were used for respiratory artifact reduction in the liver dome in a new-generation PET/CT scanner. Materials and Methods: The current study was conducted using a National Electrical Manufacturers Association International Electrotechnical Commission body phantom, with activity ratios of 2:1 and 4:1. A total of 27 patients, with respiratory artifacts in the thorax region, were analyzed. PET images were retrospectively reconstructed using either a high definition (HD) + PSF (i.e., a routine protocol) algorithm or HD+PSF+TOF (PSF+TOF; i.e., to reduce the respiratory artifact) algorithms, with various reconstruction parameters. The SUVmax and SUVmean, at different thresholds (i.e., at 45%, 50%, and 75%), were also assessed. Results: Although in comparison to the routine protocol a higher SUV was observed when using the PSF+TOF method, this approach was used to reduce the respiratory artifact. The appropriate threshold for SUV was strongly related to the lesion size, reconstruction parameters, and activity ratio. The mean of the relative difference between PSF+TOF algorithm and routine protocol for SUVmax varied from 10.58±14.99% up to 35.49±32.60% (which was dependent on reconstruction parameters). Conclusion: In comparison with other types of SUVs, the SUVmax value illustrated its significant overestimation, especially at the 4:1 activity ratio. The poor agreement between SUVmax and SUV50% was also observed. When the TOF and PSF are utilized to reduce respiratory artifacts, the SUV50% can be an accurate semi-quantitative parameter for PET/CT images, for all lesion sizes. For smaller lesions, however, a smaller filter size was required to observe an accurate SUV.


INTRODUCTION
The quantitative assessment of 18  which is widely used in evaluation of glucose metabolism, is prone to biological and technical factors (4)(5)(6). The SUVs, however, can vary depending on the method of reconstruction and parameters that are used (7)(8)(9)(10)(11). Thus, since PET images are obtained from different scanners, or even with different reconstruction methods in the same scanner, an accurate SUV is essential for reliable quantitative analysis. Previous studies have suggested different approaches to address reconstruction-dependent variation in SUVs (12)(13)(14). Furthermore, a more accurate SUV can be obtained with better spatial resolution (15,16).
The point spread function (PSF) has been used during PET reconstruction to improve the spatial resolution (17).
In our previous study (30), we showed that, in the absence of gating devices, the TOF technique can reduce the respiratory artifact in the liver dome. In the current study, we aimed to extend our results by evaluating the combination of TOF and PSF with various reconstruction parameters to choose the optimal SUV threshold for clinical PET/CT images, for accurate quantification. This evaluation was performed to quantify PET/CT images with indices consisting of SUVmax and SUVmean with various thresholds, in systematic phantom and patient studies.

Patients Population
We retrospectively assessed 27 patients (i.e., 16 men and 11 women). The patients were the same as patient group in our previous study (30).

Data Acquisition and Image Reconstruction
Following CT acquisition using smart mA technique, all emission data were obtained from the vertex to midthigh. PET images were reconstructed using a 256×256 image matrix, with 2.73 mm pixels, for the two main

Assessment Strategy
The current study aimed to obtain accurate quantification. For this purpose, the SUVmax (3D isocontour encompass the total lesion), and SUV45%, SUV50%, and SUV75% (with the mean 3D isocontour values at 45%, 50%, and 75% of the maximum voxel value, respectively) were measured in the PET images. This was repeated for all reconstruction methods for both phantom and clinical data. The relative difference for all types of SUV and mean of difference in the SUV value for various reconstruction methods and routine protocol were also calculated.

Statistical Analysis
Statistical analyses were performed using SPSS packages (SPSS, version 22.0, Armonk, NY). The Shapiro-Wilk method was utilized to test for normality. A paired ttest was used for variables with a normal distribution, while a Wilcoxon signed ranks test was conducted on nonnormally distributed data. The Lin concordance correlation coefficient (Lin CCC) was also applied to test the agreement between variables. Statistical significance was set at p<0.05. Figure 1 illustrates the comparison of the SUVmax, SUV75%, SUV50%, and SUV45% of each sphere size, between various reconstruction protocols in the phantom study.

DISCUSSION
In the current study, we utilized a NEMA IEC body phantom to obtain the optimal SUV threshold for various sphere sizes and activity ratios, with various reconstruction methods (i.e., routine protocol and PSF+TOF). In the next step, the ability of various SUV thresholds to reduce the respiratory artifact was assessed in patients with different-sized lesions in the thorax region.
Previous studies reported that using the PSF and TOF can lead to accurate quantitative analysis, with some SUV overestimation (10,11). Thus, we obtained some optional reconstruction parameters to reach the acceptable image quality in oncology patients undergoing PET/CT imaging (21,22). Variations in the reconstruction parameters and definition of the VOI for the SUV calculation can lead to discrepancies in the PET images properties and quantification analysis (28,32). In the current study, we Boellaard (33), and Kelly and Declerck (12). The SUVmax is a popular quantification parameter, which is used in 91% of diagnostic reports (34).